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Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

Srinivasan S, Vannberg FO, Dixon JB - Sci Rep (2016)

Bottom Line: Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow.Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake.Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

View Article: PubMed Central - PubMed

Affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.

ABSTRACT
It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

No MeSH data available.


Characterization of exosome uptake by CD11b and CD19 cells in the node by flow cytometry.The dominant node was digested and stained for (a) CD11b at 2 h, (c) CD11b at 2 days, (e) CD19 at 2 hours, (g) CD19 at 2 days. The non-dominant node was stained for (b) CD11b at 2 h, (d) CD11b at 2 days, (f) CD19 at 2 hours, (h) CD19 at 2 days and (i) quantitation of exosome uptake by the dominant and non-dominant nodes at 2 hours and 2 days respectively expressed as a percentage of PKH67 positive cells.
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f7: Characterization of exosome uptake by CD11b and CD19 cells in the node by flow cytometry.The dominant node was digested and stained for (a) CD11b at 2 h, (c) CD11b at 2 days, (e) CD19 at 2 hours, (g) CD19 at 2 days. The non-dominant node was stained for (b) CD11b at 2 h, (d) CD11b at 2 days, (f) CD19 at 2 hours, (h) CD19 at 2 days and (i) quantitation of exosome uptake by the dominant and non-dominant nodes at 2 hours and 2 days respectively expressed as a percentage of PKH67 positive cells.

Mentions: To determine the primary in vivo targets of exosomes, we sorted the PKH positive cells and quantified the co-localization of the exosome signal with various immune cell subset markers including CD11b (Macrophages), CD19 (B-cells) CD4 (Helper T-cells), and CD8 (Killer T- cells). CD11b is abundantly expressed on the surface of monocytes and macrophages which are situated within the subcapsular sinus of the lymph node24. Exosomes co-localized with CD11b+ macrophages in both the dominant and non-dominant lymph nodes but the dominant node had ~2 times greater macrophage-exosome co-localization as compared to the non-dominant node at 2 hours (Fig. 7a,b). Exosome localization within macrophages was reduced by half in both the dominant and non-dominant nodes from 2 hours to 2 days (Fig. 7c,d,i).


Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

Srinivasan S, Vannberg FO, Dixon JB - Sci Rep (2016)

Characterization of exosome uptake by CD11b and CD19 cells in the node by flow cytometry.The dominant node was digested and stained for (a) CD11b at 2 h, (c) CD11b at 2 days, (e) CD19 at 2 hours, (g) CD19 at 2 days. The non-dominant node was stained for (b) CD11b at 2 h, (d) CD11b at 2 days, (f) CD19 at 2 hours, (h) CD19 at 2 days and (i) quantitation of exosome uptake by the dominant and non-dominant nodes at 2 hours and 2 days respectively expressed as a percentage of PKH67 positive cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834495&req=5

f7: Characterization of exosome uptake by CD11b and CD19 cells in the node by flow cytometry.The dominant node was digested and stained for (a) CD11b at 2 h, (c) CD11b at 2 days, (e) CD19 at 2 hours, (g) CD19 at 2 days. The non-dominant node was stained for (b) CD11b at 2 h, (d) CD11b at 2 days, (f) CD19 at 2 hours, (h) CD19 at 2 days and (i) quantitation of exosome uptake by the dominant and non-dominant nodes at 2 hours and 2 days respectively expressed as a percentage of PKH67 positive cells.
Mentions: To determine the primary in vivo targets of exosomes, we sorted the PKH positive cells and quantified the co-localization of the exosome signal with various immune cell subset markers including CD11b (Macrophages), CD19 (B-cells) CD4 (Helper T-cells), and CD8 (Killer T- cells). CD11b is abundantly expressed on the surface of monocytes and macrophages which are situated within the subcapsular sinus of the lymph node24. Exosomes co-localized with CD11b+ macrophages in both the dominant and non-dominant lymph nodes but the dominant node had ~2 times greater macrophage-exosome co-localization as compared to the non-dominant node at 2 hours (Fig. 7a,b). Exosome localization within macrophages was reduced by half in both the dominant and non-dominant nodes from 2 hours to 2 days (Fig. 7c,d,i).

Bottom Line: Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow.Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake.Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

View Article: PubMed Central - PubMed

Affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.

ABSTRACT
It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

No MeSH data available.